环状 RNA 000829 通过抑制 SRSF1 介导的 SLC39A14 可变剪接发挥抑癌作用在肾细胞癌中。
Circ_000829 Plays an Anticancer Role in Renal Cell Carcinoma by Suppressing SRSF1-Mediated Alternative Splicing of SLC39A14.
机构信息
NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.
Departments of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.
出版信息
Oxid Med Cell Longev. 2022 Aug 26;2022:8645830. doi: 10.1155/2022/8645830. eCollection 2022.
BACKGROUND
Covalently closed circular RNAs (circRNAs) play critical oncogenic or anticancer roles in various cancers including renal cell carcinoma (RCC), pointing to their regulation as a promising strategy against development of RCC. We, thus, studied the tumor-suppressive role of circ_000829 in RCC through and experiments.
METHODS
The expression of circ_000829 was validated in clinical RCC tissues and RCC cell lines. Based on ectopic expression and knockdown experiments, we examined the interactions among circ_000829, serine and arginine rich splicing factor 1 (SRSF1), and solute carrier family 39 member 14 (SLC39A14, zinc transporter). Then, the effects of circ_000829, SRSF1, and SLC39A14 on cell cycle distribution and proliferation and on tumor growth were evaluated in RCC cells.
RESULTS
Circ_000829 was poorly expressed in RCC tissues and cells, while SRSF1 was highly expressed. Restoration of circ_000829 reduced the levels of SRSF1 and SLC39A14B, thereby repressing the RCC cell proliferation and tumor growth . Meanwhile, overexpression of SRSF1 and SLC39A14B promoted the proliferation and cell cycle entry of RCC cells. Mechanistically, circ_000829 directly bound to SRSF1, and SRSF1 enhanced the expression of SLC39A14B by mediating the alternative splicing of SLC39A14. SLC39A14B upregulation negated the effect of SLC39A14 knockdown on RCC cell proliferation.
CONCLUSION
Hence, this study suggests the antiproliferative role of circ_000829 in RCC growth and further elucidates the underlying mechanism involving the inhibited SRSF1-mediated alternative splicing of mRNA.
背景
共价闭合环状 RNA（circRNA）在包括肾细胞癌（RCC）在内的各种癌症中发挥关键致癌或抗癌作用，这表明对其进行调控可能是治疗 RCC 的一种有前途的策略。因此，我们通过 和 实验研究了 circ_000829 在 RCC 中的肿瘤抑制作用。
方法
在临床 RCC 组织和 RCC 细胞系中验证 circ_000829 的表达。基于外源性表达和敲低实验，我们研究了 circ_000829、丝氨酸/精氨酸丰富剪接因子 1（SRSF1）和溶质载体家族 39 成员 14（SLC39A14，锌转运体）之间的相互作用。然后，在 RCC 细胞中评估 circ_000829、SRSF1 和 SLC39A14 对细胞周期分布和增殖 以及肿瘤生长 的影响。
结果
circ_000829 在 RCC 组织和细胞中表达水平较低，而 SRSF1 表达水平较高。circ_000829 的恢复降低了 SRSF1 和 SLC39A14B 的水平，从而抑制了 RCC 细胞的增殖 和肿瘤生长 。同时，SRSF1 和 SLC39A14B 的过表达促进了 RCC 细胞的增殖和细胞周期进入。机制上，circ_000829 直接与 SRSF1 结合，SRSF1 通过介导 SLC39A14 的可变剪接增强 SLC39A14B 的表达。SLC39A14B 的上调否定了 SLC39A14 敲低对 RCC 细胞增殖的影响。
结论
因此，本研究表明 circ_000829 在 RCC 生长中的抗增殖作用，并进一步阐明了涉及抑制 SRSF1 介导的 mRNA 可变剪接的潜在机制。
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